title: Branched polyethylenimine-grafted-carboxymethyl chitosan copolymer enhances the delivery of pDNA or siRNA in vitro and in vivo.
abstract: To generate a good carrier for gene transfection, O-carboxymethyl chitosan-graft-branched polyethylenimine (OCMPEI) copolymers were synthesized by increasing the weight percentage of branched polyethylenimine conjugated to the carboxyl groups of O-carboxymethyl chitosan. These spherical polyplexes with plasmid deoxyribonucleic acid (pDNA) or small interfering ribonucleic acid (siRNA) had diameters of ~200-300 nm or ~10-25 nm, respectively, and displayed significant transfection efficiency in normal and tumor cells. In particular, expression of green fluorescent protein (GFP) following pDNA transfection was effectively suppressed by delivery of GFP-specific siRNA with the same copolymer. The optimized copolymer and polyplexes were nontoxic in vitro and in vivo. The use of endocytosis inhibitors to investigate the mechanisms of transfection of the polyplexes suggested the involvement of macropinocytosis. An in vivo study in mice showed excellent GFP expression in the lung, kidney, and liver. The results demonstrated that the OCMPEI copolymer prepared in this study is a promising carrier for in vitro and in vivo gene delivery applications.
authors.affiliation: Biomedical Polymer Laboratory, Department of Polymer Science and Engineering, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Seong-Cheol
authors.initials: SC
authors.lastname: Park
authors.forename: Joung-Pyo
authors.initials: JP
authors.lastname: Nam
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Jang
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D007097:Imines / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D011095:Polyethylenes / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D014162:Transfection / Q000379:methods*
chemical_list: D007097:Imines; D053769:Nanocapsules; D011095:Polyethylenes; D034741:RNA, Small Interfering; C505405:poly(ethylene imine); D048271:Chitosan
keywords: branched polyethylenimine; chitosan; cytotoxicity; endocytosis; gene transfection